The impact of brachytherapy boost for anal canal cancers in the era of de-escalation treatments

PURPOSETo analyze clinical outcomes of high-dose-rate (HDR) interstitial brachytherapy boost (ISBT) after external beam radiation therapy (EBRT) or chemoradiotherapy (CRT) for the treatment of anal canal cancers (ACC).METHODS AND MATERIALSA total of 78 patients with ACC were treated at our institution by ISBT. Local Control (LC), disease-free survival (DFS), overall survival (OS), colostomy-free survival (CFS) and toxicity rates were analyzed.RESULTSWith a median followup (FU) of 59.8 months (95% CI [55.8–64.2]), six (7.7%) local recurrences with 2 patients (2.6%) having persistent disease at 3 months were observed. The 5-year rate of LC for the entire population was 92% [83–96%]. The 5-year DFS rate was 86% [76–93%]. The 5-year OS was 96% [88–99%]. In the univariate analysis, chemotherapy was significantly associated with morbidity grade ≥2. Late digestive toxicity grade ≥3 was reported in 8.9% patients, 1 patient underwent colostomy due to toxicity. The 5-year CFS rate was 88% [79–94%].CONCLUSIONSHDR interstitial brachytherapy boost provide excellent rates of tumor control and colostomy-free survival with a favorable profile of GI toxicity. Continence in anal cancer survivors is a challenge and the boost technique must be discussed in a multidisciplinary approach as part of de-escalation treatments.     

Clinical outcomes of high-dose-rate brachytherapy and external beam radiotherapy in the management of clinically localized prostate cancer

PurposeTo report prostate-specific antigen (PSA) relapse-free survival and treatment-related toxicity outcomes after combining high-dose-rate (HDR) brachytherapy with external beam radiotherapy (EBRT) for patients with clinically localized prostate cancer.Methods and MaterialsBetween 1998 and 2009, 229 patients were treated with HDR brachytherapy followed 3 weeks later by supplemental EBRT. The HDR brachytherapy boost consisted of three fractions of ¹⁹²Ir (5.5–7.5 Gy per fraction), and EBRT consisted of intensity-modulated radiotherapy delivering an additional 45.0–50.4 Gy directed to the prostate gland and seminal vesicles. Median follow-up was 61 months.ResultsSeven-year PSA relapse-free survival for low-, intermediate-, and high-risk patients were 95%, 90%, and 57%, respectively (p < 0.001). Among high-risk patients treated with biological equivalent doses in excess of 190 Gy, 7-year PSA relapse-free survival was 81%. In multivariate analysis, Gleason scores of ≥8 predicted for increased risk of biochemical failure, whereas the use of short-term neoadjuvant androgen deprivation therapy did not influence tumor-control outcomes even among intermediate- or high-risk patients. Seven-year incidence of distant metastases for low-, intermediate-, and high-risk patients were 5%, 3%, and 17%, respectively. Seven-year incidence of late Grade 2 and 3 genitourinary toxicities were 22.1% and 4.9%, respectively and the 7-year incidence of Grade 2 and 3 gastrointestinal toxicities were 1% and 0.4%, respectively.ConclusionHDR prostate brachytherapy in conjunction with supplemental EBRT results in excellent biochemical relapse-free survival rates with a low incidence of severe late genitourinary or gastrointestinal toxicities. The use of short-term neoadjuvant androgen deprivation did not influence long-term biochemical tumor control in this cohort.     

Image-guided interstitial high-dose-rate brachytherapy for dose escalation in the radiotherapy treatment of locally advanced lung cancer: A single-institute experience

PurposeTo evaluate the clinical outcome after CT-guided interstitial high-dose-rate (HDR) brachytherapy for dose escalation in the radiotherapy treatment of inoperable locally advanced non–small-cell lung cancer (NSCLC).Methods and MaterialsFrom 2005 to 2015, 16 patients with unresectable NSCLC were treated. Median age was 65.7 years (range, 52–86). The median tumor volume was 95.3 cm³ (range, 20.0–2000.0). The median prescribed HDR was 15.0 Gy (range, 7.0–32.0) delivered in twice-daily fractions of 6.0–8.0 Gy in 4 patients and in once-daily fractions of 7.0–15.0 Gy in 12 patients, respectively.ResultsAfter a median followup of 12.5 months, median overall survival and local control was 12.9 and 24.9 months, respectively. The corresponding median overall survival and local control rates at 1, 2, and 3 years were 56.2%, 37.5%, and 12.5% as well as 68.9%, 57.4%, and 43%, respectively. Apart from one Grade 1 cough episode persisting for 1 week and one patient developing a minor hemopneumothorax requiring no postprocedural drainage, no other adverse events were recorded.ConclusionsCT-guided interstitial HDR brachytherapy is a safe modality for radiation dose escalation which may play a role in the definitive radiotherapy treatment of locally advanced NSCLC.     

Image-guided vulvovaginal interstitial brachytherapy in the treatment of primary and recurrent gynecological malignancies

PurposeEvaluation of interstitial high-dose-rate brachytherapy (HDRB) to the vulvovaginal region both alone and in combination with external beam radiotherapy (EBRT) for primary or recurrent gynecological malignancy.Methods and MaterialsFrom 1998 to 2009, 37 women with a mean age of 68 years were treated with transperineal interstitial HDRB. Fifteen patients (40.5%) were treated for primary disease, whereas 22 (59.5%) patients were treated for recurrent disease. Median time to local recurrence was 31 months (2–312 months). Primary sites included endometrium (12), vulva (11), vagina (10), vulvovagina (1), cervix (1), and bladder (2). Thirty-one patients (83.7%) in this series were treated with radical intent, whereas 6 (16.3%) were treated with palliative intent. Radically treated patients received between 45 and 60 Gy (median, 45 Gy) of EBRT. The median number of days from EBRT to HDR boost was 5 days (1–35 days). The HDRB doses ranged from 11 Gy in two fractions to 42 Gy in six fractions (dose per fraction varied from 4 to 8.5 Gy) and fractions were given at least 6–8 h apart.ResultsEight of the 31 patients (26%) treated with radical intent relapsed locally. Eleven of 37 patients (30%) treated with either radical or palliative intent recurred locally. The 2- and 5-year local progression-free survival was 74% and 63.4%, respectively. The total progression-free survival, which includes local, locoregional/nodal, and distant recurrence, at 2 and 5 years, was 73.6% and 45.6%, respectively. With a mean follow-up of 27 months (3.8–111.9 months), the median survival for the patient group was 16.6 months with a 2- and 5-year overall survival of 47.7% and 36.4%, respectively. Acute Grade 3 toxicity was seen in 13 (35%) of the 37 patients (skin: 10, urinary: 2, genital: 2, gastrointestinal: 0). No acute Grade 4 toxicities were seen. A total of 10 of the 37 patients (27%) developed late Grade 3 toxicities. Five of the 22 patients (22%) treated for recurrent disease with radical intent developed Grade 3 toxicity (skin: 4, urinary: 2, genital: 1, radiation-induced fracture of acetabulum: 1, and gastrointestinal: 0), whereas 1 of the 6 patients treated with palliative intent had Grade 3 toxicity affecting skin. No late Grade 4 toxicities were seen.ConclusionThis retrospective series suggests that interstitial perineal HDRB is a safe and effective treatment option for primary or locally recurrent gynecological malignancies. It is a valuable option in patients who have received previous EBRT to the pelvis, achieving good local control with acceptable late treatment-related side effects.     

High-dose-rate vs. low-dose-rate interstitial brachytherapy boost for anal canal cancers

PurposeThe purpose of this study was to analyze and compare clinical outcomes of low-dose-rate (LDR) and high-dose-rate (HDR) interstitial brachytherapy boost (ISBT) after EBRT or radio chemotherapy for the treatment of anal canal cancers.Methods and MaterialsOne hundred patients with anal canal cancers were treated at our institution by ISBT [LDR (n = 50); HDR (n = 50)]. Chronic toxicity rates, local control, disease-free survival, overall survival, and colostomy-free survival of the two different dose-rate brachytherapy modalities were analyzed and compared.ResultsWith a median followup of 42.2 months (95% CI, [34.5–48.8]), 9 (9% [4.8–16.2%]) local recurrences were observed, 4 (8% [3.2–18.8%]) in LDR vs. 5 (10% [4.4–21.4%]) in HDR group (odds ratio [OR] = 1.28 [0.32–5.07], p = 0.73). The 5-year rate of local control for the entire population was 90% [81–95%], 93% [79–98%] vs. 86% [69–94%] for LDR and HDR, respectively (p = 0.38). The 5-year disease-free survival rate for all patients was 82% [71–90%], 88% [73–95%] vs. 72% [44–88%] for LDR and HDR, respectively (p = 0.21). The 5-year overall survival rate for global population was 94% [84–98%], with no significant differences between LDR (97% [79–100%]) and HDR (93% [80–98%]) (p = 0.27). The 5-year colostomy-free survival rate was 92% [83–96%], respectively, 95% [83–99%] vs. 86% [69–94%] for LDR and HDR (p = 0.21). Significant differences were found in terms of chronic toxicity rates, with 28 (56% [42.3–68.8%]) patients concerned in low-dose-rate brachytherapy vs. 17 (34% [22.4–47.9%]) in high-dose-rate brachytherapy (OR = 0.40 [0.18–0.91], p = 0.03).ConclusionsLocal recurrence rates were comparable between both groups; HDR brachytherapy seem to have a better toxicity profile. Our data confirmed the finding that HDR can be used to safely administer ISBT without increasing chronic toxicity.     

High-dose-rate interstitial brachytherapy for vaginal endometrial cancer recurrence after prior surgery and radiotherapy

PurposeCharacterize the clinical outcomes of endometrial cancer vaginal recurrences after previous surgery and radiation therapy treated with reirradiation including image-guided interstitial high-dose-rate (HDR) brachytherapy.Methods and materialsA single-institution retrospective study identifying women receiving reirradiation for vaginal recurrence of endometrial cancer between 2004 and 2017.ResultsTwenty-three women had vaginal recurrences of endometrial cancer, median 13.7 months (range 3.5–104.9) from initial radiation. All received reirradiation with interstitial HDR brachytherapy, and seven also received external beam radiation. Median reirradiation EQD2_10 was 48 Gy (range 24.0–68.81), and median cumulative EQD2_10 was 106.25 Gy (range 62.26–122.0). Median follow-up after reirradiation was 40.2 months (range 4.5–112.7). At 3 years, overall survival was 56%, cancer-specific survival was 61%, and disease-free survival was 46%. 14 patients experienced disease recurrence; 10 including distant sites, one at a regional node only. Three patients experienced local recurrences, two of whom did not complete the prescribed course of reirradiation. The overall crude local control rate was 87%. Three patients experienced Grade 3 vaginal toxicity. There was no bladder or rectal toxicity with Grade >2.ConclusionsReirradiation including interstitial HDR brachytherapy is a promising option for vaginal recurrences of endometrial cancer after prior radiation, with high rate of local control and acceptable toxicity. However, distant failure is common. Further studies are needed to determine cumulative radiation dose limits and the role of systemic therapy in this scenario.     

The equivalent dose contribution from high-dose-rate brachytherapy to positive pelvic lymph nodes in locally advanced cervical cancer

PurposeDefinitive radiation therapy for locally advanced cervical cancer involves external beam radiation therapy (EBRT) and high-dose-rate (HDR) brachytherapy. There remains controversy and practice pattern variation regarding the optimal radiation dose to metastatic pelvic lymph nodes (LNs). This study investigates the contribution of the pelvic LN dose from HDR brachytherapy.Methods and MaterialsFor 17 patients with 36 positive pelvic LNs, each LN was contoured on a computed tomography (CT) plan for EBRT and on brachytherapy planning CTs using positron emission tomographic images obtained before chemoradiation. The mean delivered dose from each plan was recorded, and an equivalent dose in 2-Gy fractions (EQD2) was calculated. A Student's t test was performed to determine if the mean delivered dose is significantly different from the mean prescribed dose and EQD2.ResultsThe average prescribed dose from the total EBRT was 54.09 Gy. The average prescribed HDR dose to International Commission on Radiation Units point A was 26.81 Gy. The average doses delivered to the involved LNs from EBRT and brachytherapy were 54.25 and 4.31 Gy, respectively, with the corresponding EQD2 of 53.45 and 4.00 Gy. There was no statistically significant difference (p < 0.05) between the mean delivered and the prescribed doses for EBRT and between the delivered dose and the EQD2 for EBRT and brachytherapy.ConclusionsOur study shows that the HDR contribution is 7% (4.00 Gy) of the total EQD2 (57.45 Gy). The HDR contribution should be accounted for when prescribing the EBRT boost dose to pelvic LNs for the optimal therapeutic dose.     

Template-based high-dose-rate interstitial brachytherapy in gynecologic cancers: A single institutional experience

PurposeTo report the outcome and toxicities of radical external beam radiotherapy (EBRT) and template-based high-dose-rate interstitial brachytherapy (ISBT) in patients diagnosed with cervical cancer undergoing inadvertent surgery, vault cancers, and vaginal cancers at our institution.Methods and MaterialsBetween January 2000 and December 2008, 113 patients (37 patients of cervical cancer post-inadvertent surgery, 57 patients with vault cancers, and 19 patients with primary vaginal cancers) were treated with Martinez Universal Perineal Interstitial Template brachytherapy boost after EBRT. The median EBRT dose was 50 Gy, median ISBT dose was 20 Gy, whereas median total dose was 73 Gy equivalent dose at 2 Gy per fraction in all three groups.ResultsMedian followup of surviving patients for the whole group was 43 months (interquartile range, 19–67 months). The 3-year actuarial disease-free survival and overall survival for three groups was 61%, 61%, 59% and 64%, 64%, and 56%, respectively. Grade III/IV rectal toxicity was seen in 11 (10%) patients, bladder toxicity in 5 (4.5%) patients, whereas 7 (6%) patients developed Grade III small bowel toxicity. Residual disease at brachytherapy had significant impact on DFS and OS. Other factors such as age, disease volume, parametrial extension, and vaginal extension did not impact the survivals.ConclusionsMartinez Universal Perineal Interstitial Template–based high-dose-rate ISBT boost in gynecologic cancer results in a reasonable outcome in terms of survivals with acceptable late toxicities. The use of template-based ISBT is associated with a definite learning curve.     

Feasibility and Early Results of Interstitial Intensity-Modulated HDR/PDR Brachytherapy (IMBT) with/without Complementary External-Beam Radiotherapy and Extended Surgery in Recurrent Pelvic Colorectal Cancer

BACKGROUND: A new multimodality treatment concept consisting of extended resection and postoperative fractionated intensity-modulated interstitial brachytherapy (IMBT) was introduced for pelvic recurrence of colorectal carcinoma. PATIENTS AND METHODS: 46 patients received extended resection and single plastic tubes were sutured directly onto the tumor bed. IMBT was started within 2 weeks postoperatively with a median dose of 24.5 Gy (5-35 Gy). Patients were treated either with high-dose-rate brachytherapy (HDR; n = 23) or with pulsed-dose-rate brachytherapy (PDR; n = 23). 25 patients received complementary 45-Gy external-beam irradiation (EBRT) to the pelvic region after explanting the plastic tubes. RESULTS: Median follow-up was 20.6 months (7-107 months) and mean patient survival 25.7 +/- 25.8 months (median 17, range 1-107 months). After 5 years overall survival, disease-free survival and local control rate were 23%, 20% and 33%, significantly influenced by the resectional state. There was a trend in favor of PDR compared to HDR, which reached statistical significance in patients who had not received additional EBRT. CONCLUSION: The combination of extended surgery and postoperative interstitial IMBT is feasible and offers effective interdisciplinary treatment of recurrent colorectal cancer. In this small and inhomogeneous cohort of patients PDR seems to be more effective than HDR, particularly when application of complementary EBRT is not possible. None of the patients who required resection of distant metastasis survived > 2 years in this study.     

Interstitial High-Dose-Rate Brachytherapy in the Treatment of Base of Tongue Carcinoma

BACKGROUND AND PURPOSE:. To date none of the studies examined the feasibility and efficacy of interstitial high-dose-rate (HDR) brachytherapy in the treatment of carcinoma of the tongue base. Therefore the aim of this study was to contribute to this issue. PATIENTS AND METHODS:. Between 1992 and 2000 37 patients (mean age 55 years) with T1-4 and N0-3 carcinoma of the base of tongue were presented. Neck dissection was carried out in twelve cases (32%). 30 patients with advanced stage received brachytherapy boost after 50-66.5 Gy (mean, 60 Gy) locoregional external beam irradiation (EBI) and 7 patients with early stage (T1-2, N0) were managed locally with wide tumor excision and sole brachytherapy. 4 of them underwent neck dissection and the others were subjected to 50 Gy regional EBI. The mean dose of boost and sole brachytherapy was 18 Gy and 28 Gy, respectively. RESULTS:. The median follow-up time for surviving patients was 51 months. The 7 sole brachytherapy patients are living with no evidence of disease. For patients treated with EBI and brachytherapy boost, the 5-year actuarial rate of local, locoregional recurrence-free and overall survival was 60%, 52% and 46%, respectively. For all patients in univariate analysis larger tumor size (T4 vs. T1-3) was significant negative predictor of local (RR: 7.23) and locoregional control (RR: 3.87), but nodal involvement was not. Delayed soft tissue ulceration and osteoradionecrosis occurred in 4 (13%) EBI and brachytherapy treated patients. None of the sole brachytherapy patients experienced severe late radiation toxicity. CONCLUSION:. EBI combined with interstitial HDR brachytherapy boost result in acceptable local tumor control with low incidence of late side effects in patients with advanced disease. Fractionated sole HDR brachytherapy following tumor excision is a feasible treatment option for patients with early stage cancer and gives excellent local results.     

A prospective study of radical external beam radiotherapy versus external beam radiotherapy combined with intraluminal brachytherapy for primary esophageal cancer

PURPOSEThis study compared the efficacy and side effects of external beam radiotherapy (EBRT) + intraluminal brachytherapy (IBT) with EBRT alone in patients with primary thoracic esophageal cancer.MATERIALS AND METHODSBetween 2013 and 2020, 64 patients with primary thoracic esophageal cancer without surgery received radiotherapy. Thirty-two patients received EBRT + IBT. EBRT dose was 50 Gy, 2 Gy/f, 5 times a week, and IBT dose was 10 Gy, 5 Gy/f, once a week. Thirty-two patients received EBRT alone, and the total dose was 60 Gy. The median followup was 19 months.RESULTSThe local control rates (LCR) of EBRT + IBT and EBRT alone group at 1, 2, and 3 years after treatment were 88% and 72%, 53% and 22%, 25%, and 9%, respectively. The overall survival (OS) of the EBRT + IBT and EBRT alone group at 3 years after treatment were 38% and 9%. The 3-year local recurrence-free survival (LRFS) rates of EBRT + IBT and EBRT alone group were 25% and 9%. Univariate analysis showed that EBRT + IBT could be the prognostic factor improving OS (p = 0.04), and tumor located in the mid-thoracic region exhibited a poorer prognosis on LRFS (p = 0.03). Grade 3 or higher acute side effects included two cases of dysphagia and three cases of bone marrow suppression. Severe late side effects included three cases of fistula, three cases of radiation pneumonia, and five cases of stenosis requiring treatment.CONCLUSIONSCompared with EBRT alone, EBRT + IBT is an effective treatment modality for T1～3NanyM0 primary thoracic esophageal cancer with good local control. It can prolong the survival time of patients and has acceptable toxicity.     

Endobronchial brachytherapy and optimization of local disease control in medically inoperable non-small cell lung carcinoma: a matched-pair analysis

PURPOSE: External beam radiation therapy (EBRT) alone for early stage, medically inoperable non-small cell lung cancer (MILC) can produce local disease control and sometimes cure. We have previously reported that higher EBRT doses result in improved disease control and, for patients with tumors > or =3.0 cm, improved survival. This report describes the impact of dose escalation with endobronchial brachytherapy boost during or following EBRT upon local disease control. METHODS AND MATERIALS: Medical records of 404 patients with MILC treated with radiotherapy alone were reviewed. Thirty-nine patients received a planned endobronchial brachytherapy boost during or following a course of EBRT. A matched-pair analysis of disease control and survival was performed by matching each brachytherapy patient to 2 EBRT patients from a reference group of the remaining patients. RESULTS: Endobronchial brachytherapy boost significantly improved local disease control over EBRT alone (58% vs. 32% at 5 years). The local control benefit for brachytherapy was found to be limited to patients with T(1-2) disease or tumors < or =5.0 cm. Among these patients treated with endobronchial boost, EBRT doses of > or =6500 cGy were necessary to optimize local disease control. No overall survival differences were observed at 3 years. Excess toxicity with brachytherapy was not observed. CONCLUSION: Endobronchial brachytherapy boost enhances local disease control rates in MILC treated with EBRT. Local control outcome is optimized when radical EBRT doses are used in conjunction with brachytherapy.     

Clinical outcome after treatment with a brachytherapy boost versus external beam boost for anal carcinoma

PURPOSE: To evaluate the outcome after definitive whole pelvis external beam radiotherapy (EBRT) followed by brachytherapy (BT) boost after treatment break vs. external beam boost without break in the treatment of anal carcinoma. METHODS AND MATERIALS: Eighty-one consecutive patients with invasive anal carcinoma were analyzed retrospectively. Patients treated with an interstitial (192)Ir high-dose-rate (HDR) implant boost of 14Gy/7 fractions/3d given 3 weeks after completion of whole pelvis 45Gy EBRT were compared with those treated with external beam boost of 14.4Gy, started immediately after completion of whole pelvis 45Gy EBRT. Concomitant chemotherapy (CT) with mitomycin C was applied during whole pelvis EBRT depending on tumor stage. Pattern of care, local disease control (LC), cancer-specific survival (CSS), overall survival (OS), toxicity, and quality of life (QOL) were assessed. RESULTS: Radiotherapy with or without concomitant CT achieved clinical complete response in 93.4% of patients. In early stage tumors, (192)Ir-HDR BT boost with CT resulted in a 5-year LC and CSS of 100%. In all patients, BT boost did not result in improved LC, OS, and CSS compared with EBRT boost, despite stage and treatment bias favoring small tumors to be treated with BT. The 5-year and 10-year OS were 66% and 44% (BT boost) and 66% and 52% (EBRT boost), respectively. Subgroup analysis of Stages I and II disease revealed no significant improvement after BT boost compared with EBRT boost. Acute skin toxicity was less common in the BT boost group (whole cohort: p=0.14; Stages I-IIIa: p=0.05), but long-term morbidity and QOL were similar. No local necrosis was seen after BT boost and the 10-year sphincter preservation rate was 87% in these patients. CONCLUSIONS: Interstitial (192)Ir-HDR implant boost with break and EBRT boost without break yield similar results. Acute skin toxicity is reduced with BT boost but long-term morbidity and QOL are identical. BT boost is most beneficial in early stage tumors but the advantage of BT seems to be limited due to its invasiveness, doctor dependence, and logistic circumstances.     

High-dose-rate endorectal brachytherapy for locally advanced rectal cancer in previously irradiated patients

PurposePreoperative high-dose-rate (HDR) endorectal brachytherapy is well tolerated among patients with locally advanced rectal cancer. However, these studies excluded patients who previously received pelvic radiation therapy (RT). Because a favorable toxicity profile has been published for HDR endorectal brachytherapy, we evaluated this technique in patients who have previously received pelvic irradiation.Methods and MaterialsWe included patients who had received pelvic irradiation for a previous pelvic malignancy and later received preoperative HDR endorectal brachytherapy for rectal cancer. Brachytherapy was delivered to a total dose of 26 Gy in 4 consecutive daily 6.5 Gy fractions.ResultsWe evaluated 10 patients who previously received pelvic external beam radiation therapy (EBRT) alone (n=6), EBRT and brachytherapy (n=2), or brachytherapy alone (n=2). The median interval between the initial course of RT and endorectal brachytherapy was approximately 11 years (range, 1-19 years). Two patients experienced a complete pathologic response while 1 patient had a near complete pathologic response. No acute grade ≥3 toxicity was observed. No intraoperative or postoperative surgical complications were observed.ConclusionsPreoperative HDR endorectal brachytherapy is an alternative to EBRT for patients with locally advanced rectal cancer who have previously received pelvic RT.     

Efficacy of high-dose-rate interstitial brachytherapy in patients with oral tongue carcinoma

PurposeTo evaluate the results of high-dose-rate (HDR)-interstitial brachytherapy (ISBT) in oral tongue carcinomas.Methods and MaterialsBetween September 1999 and August 2007, 50 patients were treated for oral tongue carcinoma with HDR-ISBT. The patient's mean age was 58 years. Forty-two patients were in T1–2 stage and 8 patients were in T3 stage; 16 patients were in N+ stage and 34 patients in N0 stage. Exclusive ISBT was given to 17 patients (34%) in T1–2 N0 stage and complementary to external beam radiotherapy (EBRT) to 33 patients (66%). A perioperative technique was performed on 14 patients. The median total dose was 44 Gy when HDR was used alone (4 Gy per fraction) and 18 Gy when complementary to 50 Gy EBRT (3 Gy per fraction).ResultsThe median followup was 44 months. Actuarial disease-free survival rates at 3 and 5 years were 81% and 74%, respectively. Local failure developed in 7 patients. Actuarial local control (LC) rates were 87% and 79% at 3 and 5 years in T1–2 stage 94.5% and 91% and T3 stage 43% and 43% (with salvage surgery). Exclusive HDR cases showed LC in 100% of the cases, and the combined group (EBRT + HDR) showed LC in 80% and 69% of the cases at 3 and 5 years (p = 0.044). Soft-tissue necrosis developed in 16% and bone necrosis in 4% of the cases.ConclusionsHDR brachytherapy is an effective method for the treatment of oral tongue carcinoma in low-risk cases. Doses per fraction between 3 and 4 Gy yield LC and complication rates similar to low-dose rate. The perioperative technique promises encouraging results.     

Association of Brachytherapy Boost with Overall Survival for Gleason 9-10 Prostate Cancer: The Impact of Primary versus Secondary Pattern 5

PURPOSEThe addition of a brachytherapy (BT) boost to external beam radiotherapy (EBRT) reduces recurrence risk in men with high-risk prostate cancer (PCa) and may reduce PCa-mortality for Gleason grade group 5 (GG5). Whether the extent of pattern five, a risk factor for distant metastases, impacts the benefit of a BT boost is unclear.METHODSMen with localized GG5 PCa treated with (1) EBRT or (2) EBRT+BT between 2010 and 2016 were identified in the National Cancer Database. EBRT monotherapy group received conventionally fractionated (1.8−2.0 Gy per fraction) ≥74 Gy or moderately hypofractionated (2.5−3.0 Gy per fraction) ≥60 Gy. EBRT + BT group received conventionally fractionated ≥45 Gy or moderately hypofractionated ≥37.5 Gy, and either LDR or HDR BT. All patients received concomitant ADT; none received chemotherapy, immunotherapy, or surgery. OS was compared using Kaplan-Meier, log-rank test, and multivariable Cox proportional hazards in the overall cohort, followed by subgroups based on primary versus secondary pattern 5. Propensity score- and exact-matching was used to corroborate results.RESULTSA total of 8260 men were eligible: EBRT alone (89%) versus EBRT + BT (11%). 5-year OS for EBRT versus EBRT + BT was 76.3% and 85.0%, respectively (p = 0.002; multivariable adjusted HR 0.84, 95% CI 0.65−0.98; p = 0.04). These results remained consistent after propensity score and exact matching. The OS advantage of a BT boost was more prominent in men with Gleason 4 + 5 PCa (p = 0.001) and not observed in men with Gleason 5 + 5 or 5 + 4 PCa.CONCLUSIONSExtent of pattern five may be useful in appropriately selecting men for EBRT+BT and should be considered as a pre-randomization stratification variable for future clinical trial design.     

Improved survival for patients with prostate cancer receiving high-dose-rate brachytherapy boost to EBRT compared with EBRT alone

PurposeHigh-dose-rate (HDR) brachytherapy boost is a treatment of intermediate- to high-risk prostate cancer, but long-term clinical outcome data are sparse. We report long-term survival and toxicity data in a cohort of patients treated in a single institution.MethodsBetween 1998 and 2004, 654 patients with localized prostate cancer received either 3-dimensional conformal radiotherapy (median 46 Gy) with an HDR (median 18 Gy in three fractions) boost (“3-D conformal radiotherapy [3DCRT] + HDR”; 215 patients) or 3DCRT alone (“3DCRT”; median 70 Gy; 439 patients) with curative intent. Men with National Comprehensive Cancer Network intermediate risk were offered neoadjuvant androgen deprivation and with high risk were also offered adjuvant androgen deprivation. Data collection included patient-reported outcome measures.ResultsThe 3DCRT + HDR group was older (72.3 vs. 68.9 yrs), had higher presenting PSAs (iPSA) (15.66 and 12.57 ng/mL, respectively), higher proportion of Gleason scores >7 (15.3% vs. 12.4%), and higher proportions of extracapsular disease (29.3% vs. 25.5%). 3DCRT + HDR men had lower proportions of low-risk patients (3.3% vs. 19.4%) and higher proportions of high-risk patients (50.7% vs. 37.4%) than the 3DCRT group. The 5-, 10-, and 15-year overall survival was superior at 92%, 81%, and 67%, respectively, for the 3DCRT + HDR group, compared with 88%, 71%, and 53%, respectively, in the 3DCRT group (p < 0.001). The 5-, 10-, and 15-year cause specific survival also favored the HDR boost group with survival of 96%, 93%, and 87% (3DCRT + HDR) and 95% 88% and 79% (3DCRT), respectively (p < 0.037).ConclusionsHDR brachytherapy boost in conjunction with 3DCRT offered superior overall survival and cause-specific survival in our patient population.     

Addition of intracavitary brachytherapy to external beam radiation therapy for T1–T2 nasopharyngeal carcinoma

PurposeWe compared efficacy and toxicity outcomes of patients with T1–T2 nasopharyngeal carcinoma (NPC) treated with external beam radiation therapy (EBRT) in combination with intracavitary brachytherapy (BT) vs. a historical cohort treated with EBRT alone.Methods and MaterialsOf the 348 NPC patients diagnosed with T1–2N0–3M0 disease, 175 received EBRT + BT and 173 received EBRT alone. For the EBRT + BT group, median dose of EBRT was 58 Gy and median dose of BT was 20 Gy; for the EBRT group, median dose was 72 Gy (range, 60–82.4 Gy). Measured outcomes included 5- and 10-year local control (LC), regional failure–free survival, distant metastasis–free survival, disease-free survival, overall survival (OS), and late toxicity.ResultsMedian followup duration was 120 months (range, 5–190). Ten-year OS and LC rates for the EBRT + BT and EBRT-alone groups were 71.7% vs. 49.9% and 94.0% vs. 85.2%, respectively (χ² = 21.273, p = 0.000 for OS and χ² = 4.684, p = 0.030 for LC). Late complication rates for EBRT + BT were generally lower compared with the EBRT-alone group except for nasopharyngeal ulceration or necrosis, where the rate was higher but not statistically significant. Both stage of disease at diagnosis and treatment techniques (i.e., the use of BT) were significant predictive factors for OS and LC.ConclusionIntracavitary BT in combination with EBRT may improve the therapeutic ratio for T1–T2 NPC.     

Clinical outcomes of high-dose-rate interstitial gynecologic brachytherapy using real-time CT guidance

PurposeTo evaluate clinical outcomes of CT-guided high-dose-rate (HDR) interstitial brachytherapy for primary and recurrent gynecologic cancer.Methods and MaterialsRecords were reviewed for 68 women (34 with primary disease and 34 with recurrence) treated with CT-guided HDR interstitial brachytherapy between May 2005 and September 2011. Interstitial application was performed under general anesthesia using an iterative approach of catheter insertion and adjustment with serial image acquisition by CT in a dedicated brachytherapy suite. The median fractional brachytherapy dose was 3.9 Gy delivered twice daily in seven fractions. The median cumulative dose in equivalent 2-Gy fractions was 74.8 Gy. Actuarial survival estimates were calculated using the Kaplan–Meier method, and toxicity was reported by Common Toxicity Criteria.ResultsPrimary disease sites were endometrial (34), cervical (17), vaginal (11), ovarian (3), and vulvar (3). Median age was 61.5 years, and tumor size at diagnosis was 3.4 cm. Median D₉₀ and V₁₀₀ were 73.6 Gy and 87.5%, respectively; median D_2cc for bladder, rectum, and sigmoid were 67.1, 64.6, and 53.7 Gy, respectively. With a median followup of 17 months, actuarial rates of local control, progression-free survival, and overall survival at 2 years for all patients were 86%, 60%, and 64%, respectively. There were 9 grade 3 late toxicities (six gastrointestinal and three vulvovaginal).ConclusionsHDR interstitial brachytherapy with CT-guided catheter placement results in acceptable local control, toxicity, and survival rates for women with primary or recurrent gynecologic cancer. Durable pelvic control may be achieved in most patients with this specialized brachytherapy technique.     

Neoadjuvant Interstitial High-Dose-Rate (HDR) Brachytherapy Combined with Systemic Chemotherapy in Patients with Breast Cancer

BACKGROUND AND PURPOSE: This is the first study investigating neoadjuvant interstitial high-dose-rate (HDR) brachytherapy combined with chemotherapy in patients with breast cancer. The goal was to evaluate the type of surgical treatment, histopathologic response, side effects, local control, and survival. PATIENTS AND METHODS: 53 patients, who could not be treated with breast-conserving surgery due to initial tumor size (36/53) or due to an unfavorable breast-tumor ratio (17/53), were analyzed retrospectively. All but one were in an intermediate/high-risk group (St. Gallen criteria). The patients received a neoadjuvant protocol consisting of systemic chemotherapy combined with fractionated HDR brachytherapy (2 x 5 Gy/day, total dose 30 Gy). In cases, where breast-conserving surgery was performed, patients received additional external-beam radiotherapy (EBRT, 1.8 Gy/day, total dose 50.4 Gy). In patients, who underwent mastectomy but showed an initial tumor size of T3/T4 and/or more than three infiltrated lymph nodes, EBRT was also performed. RESULTS: In 30/53 patients (56.6%) breast-conserving surgery could be performed. The overall histopathologic response rate was 96.2% with a complete remission in 28.3% of patients. 49/53 patients were evaluable for follow-up. After a median of 58 months (45-72 months), one patient showed a mild fibrosis of the breast tissue, three patients had mild to moderate lymphatic edema of the arm. 6/49 (12.2%) patients died of distant metastases, 4/49 (8.2%) were alive with disease, and 39/49 (79.6%) were free from disease. Local recurrence was observed in only one case (2%) 40 months after primary therapy. After mastectomy, this patient is currently free from disease. CONCLUSION: The combination of interstitial HDR brachytherapy and chemotherapy is a well-tolerated and effective neoadjuvant treatment in patients with breast cancer. Compared to EBRT, treatment time is short. Postoperative EBRT of the whole breast -- if necessary -- is still possible after neoadjuvant brachytherapy. Even though the number of patients does not permit definite conclusions, the results are promising regarding survival and the very low rate of local recurrences.